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Resveratrol inhibits Extranodal NK/T cell lymphoma through activation of DNA damage response pathway

Xianxian Sui1, Canjing Zhang2, Jianan Zhou3

  • 1Department of Physiology & Pathophysiology, School of Basic Medical Sciences, Fudan University, Shanghai, China.

Journal of Experimental & Clinical Cancer Research : CR
|September 28, 2017
PubMed
Abstract

Insights

Resveratrol (RSV) inhibits extranodal NK/T cell lymphoma (NKTCL) cell growth by inducing apoptosis and activating the DNA damage response (DDR) pathway. This natural compound shows promise as a potential anti-cancer drug for NKTCL treatment.

Area of Science:

  • Oncology
  • Molecular Biology
  • Pharmacology

Background:

  • Extranodal NK/T cell lymphoma (NKTCL) is an aggressive non-Hodgkin lymphoma with a poor prognosis.
  • Resveratrol (RSV), a natural compound from grapes, exhibits various bioactivities, including anticarcinogenic effects.
  • This study investigates the anti-tumor potential of RSV in NKTCL cell lines.

Purpose of the Study:

  • To evaluate the anti-tumor effect of Resveratrol (RSV) on Extranodal NK/T cell lymphoma (NKTCL) cell lines.
  • To elucidate the molecular mechanisms underlying RSV's anti-cancer activity in NKTCL.
  • To explore the role of the DNA damage response (DDR) pathway in RSV-induced NKTCL apoptosis.

Main Methods:

  • RSV was applied to NKTCL cell lines (SNT-8, SNK-10, SNT-16) to assess its effects on proliferation and apoptosis.
  • Mitochondrial apoptosis pathway markers (Mcl-1, survivin, Bax, Bad, caspases) and signaling pathways (AKT, Stat3) were analyzed.
  • The DNA damage response (DDR) pathway, including ATM/Chk2/p53, was investigated using specific inhibitors and in combination with other treatments.

Main Results:

  • RSV inhibited NKTCL cell proliferation in a dose- and time-dependent manner, arresting the cell cycle at the S phase.
  • RSV induced apoptosis via the mitochondrial pathway, evidenced by altered expression of apoptosis-related proteins and caspase activation.
  • RSV suppressed AKT and Stat3 phosphorylation and activated the DDR pathway, which was crucial for NKTCL cell apoptosis.

Conclusions:

  • RSV demonstrates significant in vitro anti-tumor effects against NKTCL cell lines.
  • The anti-tumor activity of RSV is mediated through the activation of the ATM/Chk2/p53-dependent DNA damage response pathway.
  • RSV warrants further investigation as a potential therapeutic agent for Extranodal NK/T cell lymphoma.
Keywords:
DNA damage response pathwayEpstein-Barr virusExtranodal NK/T cell lymphomaResveratrolZtapATM

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